Mitochondrial HealthAnti-AgingEnergy EnhancementMetabolic Support
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) and NAD+ (Nicotinamide Adenine Dinucleotide) represent a powerful combination for enhancing mitochondrial function, energy production, and longevity. When administered subcutaneously, these compounds work synergistically to combat age-related cellular decline and optimize metabolic health.
Understanding MOTS-c and NAD+
MOTS-c is a 16-amino-acid peptide derived from the mitochondrial genome, known for its role in regulating metabolism, energy production, and cellular stress responses. This remarkable peptide acts as a signaling molecule that enhances mitochondrial function and promotes cellular health.
NAD+ is a vital coenzyme involved in redox reactions, DNA repair, and mitochondrial function. Unfortunately, NAD+ levels naturally decline with age by approximately 50% by age 50, making supplementation increasingly important for maintaining optimal cellular function.
When administered subcutaneously, both compounds can work together synergistically, as MOTS-c has been shown to naturally elevate NAD+ levels, creating an amplified effect for metabolic health, anti-aging, and energy optimization.
Individual Benefits
MOTS-c Benefits (5-10 mg weekly subcutaneous)
Improved Metabolic Function: Enhances glucose uptake in skeletal muscle, reduces insulin resistance, and promotes fat metabolism
Anti-Aging Protection: Boosts mitochondrial respiration, reduces inflammation and oxidative stress
Muscle and Bone Health: Improves muscle function, exercise performance, and bone metabolism
Immune Support: Enhances immune responses and helps cells adapt to metabolic stress
NAD+ Benefits (100-500 mg, 2-3 times weekly subcutaneous)
Enhanced Energy Production: Boosts ATP production, combats fatigue, and supports cellular energy
Anti-Aging and DNA Repair: Activates sirtuins (SIRT1) for epigenetic regulation and longevity
Cognitive Support: Improves mental clarity, aids detoxification, and accelerates recovery
Metabolic Health: Supports weight management, insulin signaling, and cardiovascular function
Synergistic Benefits of the Combination
1. Boosted Mitochondrial Function and Energy Production
MOTS-c elevates intracellular NAD+ levels (which naturally decline ~50% by age 50), amplifying NAD+'s role in ATP synthesis and mitochondrial biogenesis. Together, they may improve cellular energy, reduce fatigue, and enhance exercise tolerance through AMPK and SIRT1 pathway activation.
2. Enhanced Anti-Aging and Longevity
The combination targets age-related NAD+ depletion, with MOTS-c mitigating shortages via JAK and folate/methionine cycles. This may slow cellular senescence, support DNA repair, and reduce oxidative stress/inflammation, potentially extending healthspan.
3. Improved Metabolic Health and Insulin Regulation
Synergy in enhancing insulin sensitivity, glucose metabolism, and fat loss. MOTS-c boosts NAD+-dependent SIRT1 for better glycolytic effects, potentially aiding in obesity, diabetes, and metabolic syndrome management.
4. Reduced Inflammation and Cellular Protection
Combined action combats oxidative stress, supports immune clearance of damaged cells, and protects against age-related diseases. Enhanced DNA repair and stress adaptation capabilities.
Evidence and Mechanism Summary
Benefit Category
Synergistic Mechanism
Evidence Level
Energy & Mitochondria
MOTS-c ↑ NAD+ → AMPK/SIRT1 activation
Preclinical (mice), mechanistic studies
Anti-Aging
NAD+ elevation delays senescence
Observational (human longevity), animal models
Metabolism
Improved insulin via shared pathways
In vitro & in vivo (diabetes models)
Inflammation
Reduced oxidative stress/DNA damage
Cell studies, limited human data
Dosage and Administration
Typical Subcutaneous Dosing Protocols
MOTS-c: 5-10 mg weekly subcutaneous injection
NAD+: 100-500 mg, administered 2-3 times weekly subcutaneously
This educational content is from 2025 research sources. MOTS-c and NAD+ are research compounds.
Seek medical advice for personalized protocols and consider using tools like Peptide Health Tracker for monitoring.